The present invention is generally in the field of methods and compositions to neutralize or treat biologicals used especially in bioterrorism or biological warfare.
Prevention of death and disease from biological warfare agents is a concern for people serving the military and for civilians. Agents used in biological warfare include nerve gases, anthrax, ricin, botulinus, cholera, tularemia, and bubonic plague.
Atropine is a nerve gas antidote. Presently, it is delivered either by injection or via the pulmonary route employing a pressurized metered dose inhaler (PMDI). Individuals who are not practiced in self-injection frequently show reluctance to self-administer a drug via injection, let alone during times of stress, such as when under attack with a chemical agent. More importantly, pulling such a device out of a pack and moving all of the clothing and other paraphernalia to reach an appropriate site for injection incurs an unacceptable delay in time of treatment.
While the PMDI does not require self-injection, it has a number of limitations. First, the PMDI can only be used effectively over a restricted temperature range (i.e. 52° F.–86° F.), and as a result is inappropriate for use in desert conditions, or in cold environments. Second, the PMDI cannot be used at high altitudes. Third, the PMDI requires the user to synchronize his breathing with the release of the pressurized aerosol to achieve an appropriate and reproducible dose. Most people have not practiced this technique and in an emergency situation would not successfully administer the necessary dose of atropine.
Anthrax disease is caused by a potent lethal exotoxin, secreted by the bacteria to its local environment. Bacillus anthracis, the etiologic agent of anthrax, is a large, gram-positive, nonmotile, spore-forming bacterial rod. The three virulence factors of B. anthracis are edema toxin, lethal toxin and a capsular antigen. B. anthracis is a highly lethal biological warfare agent. It is relatively easy to make, store, and use as a weapon.
If untreated, anthrax can lead to septicemia and death. Inhalational anthrax is virtually always fatal. Case-fatality rates for inhalational anthrax are thought to approach 90 to 100%. (Center for Disease Control, Atlanta, Ga.). Methods which are effective to immediately mitigate or avoid the pathogen's destruction ability (exotoxin) are essential. These may include administration of antibodies and/or antibiotic directly into the lungs, or other agents which block the action of the exotoxin. However, means to accomplish this are not currently available.
It is therefore an object of the invention is to provide compositions which can be administered before or after exposure to an agent of biological warfare to prevent death and/or infection.
A further object of the invention to provide methods for self-administration of the compositions in an emergency situation.
A further object of the invention is to provide methods for effectively immunizing individuals via the pulmonary system against agents of biological warfare.